Cited by 46Cell death mechanisms and regulationCancer-related Molecular PathwaysHeat shock proteins research

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Induction of apoptosis and/or necrosis following exposure to antitumour agents in a melanoma cell line, probably through modulation of Bcl-2 family proteins

Abstract

Malignant melanoma cells have been reported to be highly resistant to chemotherapeutic agents. To gain insight into the molecular mechanisms underlying chemotherapeutic drug resistance, we examined the role of the Bcl-2 family members Bcl-2 and Bax in cell death in the melanoma cell line G361 following stimulation with cisplatin (CDDP) or dacarbazine (DTIC). Trypan blue dye exclusion showed that both CDDP and DTIC induced death of G361 cells. Apoptotic and necrotic cell death could be distinguished by flow cytometry using combined staining with annexin V and 7-amino-actinomycin D (7-AAD). CDDP-induced cell death at a low concentration (0.6 micro g/ml) was mainly due to apoptosis (annexin V+/7-AAD-), while a mixture of apoptosis and secondary necrosis (annexin V+/7-AAD+) was found at a high concentration (6 micro g/ml). DTIC at the concentrations used induced only apoptosis. CDDP-induced apoptosis and secondary necrosis were accompanied by activation of caspase-3 and modulation of Bcl-2 family members Bcl-2 and Bax. On Western blotting Bax was seen to be upregulated with concomitant downregulation of Bcl-2. Flow cytometry, which enables measurement of protein at the single-cell level, revealed that Bcl-2+/Bax- cells were decreased, with a slight concomitant rise in Bcl-2-/Bax+ cells on stimulation with CDDP. These findings suggest that the chemotherapeutic agents CDDP and DTIC induce apoptosis and/or secondary necrosis depending on dose, probably involving the modulation of Bcl-2 family proteins.

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Crossref · 10.1097/00008390-200310000-00004

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Research works printed but not linked: 5

  1. Di Felice, 1998, Int J Oncol, 13, 225
  2. Kim, 1999, Int J Oncol, 15, 751
  3. Miyashita, 1992, Cancer Res, 52, 5407
  4. Searle, 1982, Pathol Annu, 17, 229
  5. Eguchi, 1997, Cancer Res, 57, 1835

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Metadata

Authors
Shibuya, H., Kato, Y., Saito, M., Isobe, T., Tsuboi, R., Koga, M., Toyota, H., & Mizuguchi, J.
Affiliations
  • Tokyo Medical University (JP)
  • Tokyo Medical University Hospital (JP)
Corresponding author
Mizuguchi, Junichiro
Venue
Melanoma Research
Published
2003-10
Volume
13
Issue
5
Pages
457-464
ISSN
0960-8931 (ISSN-L)
OpenAlex
W2000352929
Cited by
46
References
39
Citations by year
2026: 1 · 2025: 1 · 2024: 2 · 2022: 1 · 2021: 2 · 2019: 1 · 2017: 1 · 2015: 2 · 2014: 2 · 2013: 1 · 2012: 2
FWCI
0.92
Type
journal article
Language
en
Open access
closed
Locations
  • Melanoma Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
  • Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
Keywords
melanoma, apoptosis, secondary necrosis, Bcl-2 family proteins, Bcl-2, Bax, cisplatin, dacarbazine, chemoresistance, caspase-3, dose-dependent cell death
MeSH terms
Antineoplastic Agents, Cell Survival, Cisplatin, Dacarbazine, Dactinomycin, Dose-Response Relationship, Drug, Coloring Agents, Enzyme Activation, Flow Cytometry, Fluorescent Dyes, Humans, Melanoma, Necrosis, Time Factors, Trypan Blue, Blotting, Western, Down-Regulation, Up-Regulation, Cell Death, Apoptosis, Annexin A5, Antineoplastic Agents, Alkylating, Proto-Oncogene Proteins c-bcl-2, Caspases, Cell Line, Tumor, Caspase 3

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